Among the scientific publications in the clonidine art, exemplary are P. B. Timmermanns et al., J. Med. Chem. 20 1636 (1977) and J. P. Hieble et al., Arch. Pharmacol. 309 217 (1979). Timmermanns is a detailed structure function analysis of this class of compounds in which he concludes at column 2, page 1643, that the para or 4-position "should be left unsubstituted".
Recently, A. DeJonge et al., J. Pharmacol. Exp. Ther., 222, 705 (1982) reported that a bulky substituent such as a chloro at the 5-position of a 2-phenyl iminoimidazolidine favors peripheral .alpha..sub.1 receptor agonism over central receptor agonism. This publication is not a reference against the present invention.
The compound of the invention goes against the teaching of the art to give a compound whose qualitative biological activities differ significantly from those of clonidine. Clonidine (2-(2,6-dichlorophenylimino)-2-imidazolidine) is a potent anti-hypertensive, sedative agent which has led to extensive structure-activity examination of the series of phenylimino-2-imidazolidines.
U.S. Pat. Nos. 3,236,857 and 3,454,701 are examples of many publications in this art. Among the species specifically disclosed here is 2(4-tert.-butyl-2-chlorophenyl-imino)-2-imidazolidine, column 6, line 25 of U.S. Pat. No. 3,454,701. These two patents disclose no particular advantage of a 4-tert.-butyl pharmacophore. In fact, clonidine, itself, is mentioned as the most active and least toxic of the series, see column 10 of the latter patent.
It is believed that the compound of this invention as well as its unique biological spectrum are not taught in the prior art and that, in fact, the state of prior art would lead one skilled in the art away from preparing the compound.